Glioblastoma is the most common malignant primary central nervous system tumor and one of the most debilitating cancers. The prognosis of patients with glioblastoma remains poor, and the management of this tumor, both in its primary and recurrent forms, remains suboptimal. Despite the tremendous efforts that are being put forward by the research community to discover novel efficacious therapeutic agents and modalities, no major paradigm shifts have been established in the field in the last decade. However, this does not mirror the abundance of relevant findings and discoveries made in preclinical glioblastoma research. Hence, developing and utilizing appropriate preclinical models that faithfully recapitulate the characteristics and behavior of human glioblastoma is of utmost importance. Herein, we offer a holistic picture of the evolution of preclinical models of glioblastoma. We further elaborate on the commonly used in vitro and vivo models, delving into their development, favorable characteristics, shortcomings, and areas of potential improvement, which aids researchers in designing future experiments and utilizing the most suitable models. Additionally, this review explores progress in the fields of humanized and immunotolerant mouse models, genetically engineered animal models, 3D in vitro models, and microfluidics and highlights promising avenues for the future of preclinical glioblastoma research.

Background: The proximity of transverse sinus stenosis (TSS) to inner ear structures and the temporal bone makes it a substantial cause of pulsatile tinnitus (PT). Treatment typically involves venous sinus stenting. This study investigates the hemodynamic stressors in TSS patients with PT along the pulse-transmitting temporal bone area and evaluates its treatment effects. Methods: Four patients with idiopathic intracranial hypertension, PT, and TSS, and four control patients were imaged using MR venography (MRV) and flat panel CT (FP-CT). Patient-specific blood flow simulations were conducted using boundary conditions based on quantitative MR angiography before and after VSS. Catheter-based trans-stenotic pressure gradient measurements were used to validate the simulation results. Results: The prediction of pressure gradients was close to catheter-based measurements using FP-CT-based segmentations (absolute deviation of 0.35 mm Hg) and is superior to MRV-based reconstructions (absolute deviation of 6.9 mm Hg). In TSS patients, the sinus temporal bone contact areas revealed notably higher time-averaged wall shear stress by 47±22% and velocity values by 41±18% compared with the sinus brain side. The relative residence time decreased by 57±58%. After stenting, the hemodynamic parameters dropped at the temporal side and throughout the sigmoid sinus. Almost all control patient hemodynamics remained lower than post-interventional results. Conclusion: Our simulations based on patient-specific flows highly predicts pressure gradients across the stenosis. Flow conditions in TSS reveal flow jet formation and high shear rates at the temporal bone, potentially causing sound transmission. The treatment reduces these stressors, demonstrating its targeted therapeutic effect.

Background: The concurrent presentation of meningioma and intracranial aneurysm (IA) poses diagnostic and therapeutic challenges, with no standardized management protocol available. This study aims to address this through an updated systematic review, delineating optimal strategies for managing this dual pathology.Methods: A systematic review was conducted across PubMed, Web of Science, and Embase databases. Articles were screened independently by two reviewers. Treatment strategies and patient outcomes were comprehensively analyzed to formulate a treatment framework based on several characteristics. In addition, one concurrent meningioma and IA case from our institution was presented.Results: A total of 69 articles comprising 115 patients were included in the study. The cohort exhibited a female predominance (80%) with a mean age of 56 (±13) years. Meningiomas were primarily localized to the frontotemporal and sellar regions, while aneurysms favored the anterior circulation – notably, 16.5% of cases presented with ruptured aneurysms. Management strategies varied based on the spatial relationship between lesions and aneurysm rupture status. In unruptured cases, 34% underwent a single craniotomy for simultaneous resection of both pathologies, while endovascular intervention was favored when the IA originated from an artery feeding the meningioma (73%). Remarkably, postoperative aneurysm rupture occurred in 33% of cases managed solely through tumor resection (range 0–30 days postop).Conclusion: This study proposes a comprehensive treatment algorithm to guide neurosurgeons in managing concurrent meningioma and IA cases. By considering individual patient intricacies, the feasibility of simultaneous management, aneurysm rupture risk, and symptomatology, this framework is a valuable tool for clinical decision-making in these complex scenarios.

Background/Objectives: Intracranial arteriovenous malformations (AVMs) exhibit a complex vasculature characterized by a locally occurring tangled nidus connecting the arterial and venous system bypassing the capillary network. Clinically available imaging modalities may not give sufficient spatial or temporal resolution. Adequate 3D models of large vascular areas and a detailed blood flow analysis of the nidus including the surrounding vessels are not available yet. Methods: Three representative AVM cases containing multimodal image data (3D rotational angiography, magnetic resonance angiography, magnetic resonance venography, and phase-contrast quantitative magnetic resonance imaging) are investigated. Image segmentation results in partial 3D models of the different vascular segments, which are merged into large-scale neurovascular models. Subsequently, image-based blood flow simulations are conducted based on the segmented models using patient-specific flow measurements as boundary conditions. Results: The segmentation results provide comprehensive 3D models of the overall arteriovenous morphology including realistic nidus vessels. The qualitative results of the hemodynamic simulations show realistic flow behavior in the complex vasculature. Feeding arteries exhibit increased wall shear stress (WSS) and higher flow velocities in two cases compared to contralateral vessels. In addition, feeding arteries are exposed to higher overall WSS with increased value variation between individual vessels (20.1 Pa ± 17.3 Pa) compared to the draining veins having a 62% lower WSS (8.9 Pa ± 5.9 Pa). Blood flow distribution is dragged towards the dominating circulation side feeding the nidus for all the cases quantified by the volume flow direction changes in the posterior communicating arteries. Conclusions: This multimodal study demonstrates the feasibility of the presented workflow to acquire detailed blood flow predictions in large-scale AVM models based on complex image data. The hemodynamic models serve as a base for endovascular treatment modeling influencing flow patterns in distally located vasculatures.

Idiopathic intracranial hypertension (IIH) is traditionally characterized by elevated intracranial pressure without an identifiable cause, primarily affecting obese women. However, recent evidence suggests that venous sinus stenosis may play a significant role in the pathophysiology of IIH, challenging its designation as “idiopathic.” This editorial discusses the limitations of the current nomenclatures and diagnostic criteria, highlighting the importance of routine venography in detecting venous sinus abnormalities, irrespective of a patient's demographic profile. We propose a new nomenclature of this subset of patients to venous sinus stenosis intracranial hypertension in order to promote more accurate diagnosis and targeted treatment, including potential endovascular interventions.